Clinical characteristics, gene mutations and enzyme replacement therapy of 13 children with Pompe disease / 中华实用儿科临床杂志

Objective:To summarize the clinical features, gene mutations and experience of standardized enzyme replacement therapy (ERT) of Pompe disease (PD) in children.Methods:A retrospective analysis was performed on the clinical data of 13 children with PD, who were hospitalized in Qingdao Women and Children′s Hospital from December 2016 to August 2021.According to the age at onset, the children were divided into the infantile-onset Pompe disease (IOPD) group and late-onset Pompe disease (LOPD) group.At the same time, they were divided into the ERT group and non-ERT group according to whether recombinant human acid alpha-glucosidase (rhGAA) was infused.Furthermore, the ERT group was divided into the standard ERT group and non-standard ERT group.The standard ERT group received a dose of 20 mg/kg every 2 weeks for 52 weeks.The survival rate was compared between groups by using the Kaplan-Meier method.Results:Among the 13 children with PD, there were 7 males and 6 females.Ten cases belonged to the IOPD group and 3 cases belonged to the LOPD group.The most common cause of initial consultation in the IOPD group was cardiac involvement, which accounted for 60.0% (6/10 cases), while the LOPD group mainly presented with myasthenia, cardiac involvement and respiratory tract infection at the first diagnosis.The serum level of creatine kinase (CK) in all cases increased to varying degrees.Acid alpha-glucosidase (GAA) was completely deficient in 1 case and decreased in 12 cases.All the children in the IOPD group showed myocardial hypertrophy, electrocardiograph (ECG) suggested a short PR interval, increased QRS voltage and extensive T-wave inversion.Three new mutations were found by GAA gene analysis, and they were c. 1861T>G (p.Trp621Gly), c.2278A>T (p.K760X), and c. 949G>A (p.A317T). Five cases in the IOPD group were given ERT.Two of them were given standard ERT for 52 weeks, and the other 3 cases were treated with non-standard ERT.At the end of follow-up, 2 cases treated with standardized ERT survived and the remaining 8 cases died of heart failure or respiratory failure.In the LOPD group, only 1 case was given ERT one time.Finally, 2 cases survived and one died of respiratory failure.The total fatality rate was 69.2%(9/13 cases). The survival rate of the ERT group (50.0%) and standard ERT group (100.0%) was significantly higher than that of the non-ERT group (14.3%) ( Log Rank P=0.037, 0.044). Conclusions:The clinical manifestations of PD are diverse.GAA activity examination and GAA gene analysis are important for clinical diagnosis of PD.Standardized ERT can significantly delay the progression of PD and even reverse myocardial hypertrophy in children with IOPD.

Clinical characteristics, gene mutations and enzyme replacement therapy of 13 children with Pompe disease / 中华实用儿科临床杂志

Objective:To summarize the clinical features, gene mutations and experience of standardized enzyme replacement therapy (ERT) of Pompe disease (PD) in children.Methods:A retrospective analysis was performed on the clinical data of 13 children with PD, who were hospitalized in Qingdao Women and Children′s Hospital from December 2016 to August 2021.According to the age at onset, the children were divided into the infantile-onset Pompe disease (IOPD) group and late-onset Pompe disease (LOPD) group.At the same time, they were divided into the ERT group and non-ERT group according to whether recombinant human acid alpha-glucosidase (rhGAA) was infused.Furthermore, the ERT group was divided into the standard ERT group and non-standard ERT group.The standard ERT group received a dose of 20 mg/kg every 2 weeks for 52 weeks.The survival rate was compared between groups by using the Kaplan-Meier method.Results:Among the 13 children with PD, there were 7 males and 6 females.Ten cases belonged to the IOPD group and 3 cases belonged to the LOPD group.The most common cause of initial consultation in the IOPD group was cardiac involvement, which accounted for 60.0% (6/10 cases), while the LOPD group mainly presented with myasthenia, cardiac involvement and respiratory tract infection at the first diagnosis.The serum level of creatine kinase (CK) in all cases increased to varying degrees.Acid alpha-glucosidase (GAA) was completely deficient in 1 case and decreased in 12 cases.All the children in the IOPD group showed myocardial hypertrophy, electrocardiograph (ECG) suggested a short PR interval, increased QRS voltage and extensive T-wave inversion.Three new mutations were found by GAA gene analysis, and they were c. 1861T>G (p.Trp621Gly), c.2278A>T (p.K760X), and c. 949G>A (p.A317T). Five cases in the IOPD group were given ERT.Two of them were given standard ERT for 52 weeks, and the other 3 cases were treated with non-standard ERT.At the end of follow-up, 2 cases treated with standardized ERT survived and the remaining 8 cases died of heart failure or respiratory failure.In the LOPD group, only 1 case was given ERT one time.Finally, 2 cases survived and one died of respiratory failure.The total fatality rate was 69.2%(9/13 cases). The survival rate of the ERT group (50.0%) and standard ERT group (100.0%) was significantly higher than that of the non-ERT group (14.3%) ( Log Rank P=0.037, 0.044). Conclusions:The clinical manifestations of PD are diverse.GAA activity examination and GAA gene analysis are important for clinical diagnosis of PD.Standardized ERT can significantly delay the progression of PD and even reverse myocardial hypertrophy in children with IOPD.

Application of double coronary artery guide-wires for establishing complex pathway of interventional therapy for congenital heart diseases / 中国介入影像与治疗学

Objective: To explore the application value of double coronary artery guide-wire method in establishment complex pathway of interventional therapy for congenital heart diseases (CHD). Methods: Clinical data of 12 children with CHD were retrospectively analyzed, including 5 patients with pulmonary artery stenosis after correction of pulmonary atresia with ventricular septal defect (PA/VSD), 1 with pulmonary artery stenosis after radical repair of tetralogy of Fallot (TOF), 1 with pulmonary artery stenosis after correction of transposition of great artery (TGA), 3 patients with pulmonary atresia with major aorta pulmonary collateral arteries (MAPCAs), 1 with complex pulmonary arteriovenous fistula (PAVF) and 1 with circumflex branch of left coronary artery-right atrial fistula. The characteristics of complex pathways for interventional treatment of CHD were analyzed. Results: The pathways were successfully established with double coronary artery guide-wires in all patients. Balloon intervention was successfully performed in patients with pulmonary artery stenosis after correction of PA/VSD, radical repair of TOF and TGA underwent. Patients with pulmonary atresia with MAPCAs, complex PAVF and circumflex branch of left coronary artery-right atrial fistula underwent successfully occlusion. No major complication, such as valvular injury, vascular injury, pericardial tamponade or death occurred. Conclusion: Double coronary artery guide-wire method is safe and effective for establishing complex pathway of interventional therapy for congenital heart diseases, which has strong flexibility and can provide sufficient support through tortuous pathway to improve the successful rate of intervention, therefore being worthy of clinical popularization and application.

Surgical treatment of pulmonary atresia with intact ventricular septum / 国际儿科学杂志

Pulmonary atresia with intact ventricular septum(PA/IVS) is one of the complicated cyanotic congenital heart diseases with high mortality,which needs early intervention after birth.With further understanding of the disease and the development of surgery,the operative plan of the disease is gradually changing and some fundamental changes have taken place.The hemodynamic awareness of the disease is an important factor in the selection of surgery and the improvement of prognosis.In addition,it is also important for the selection of surgery and the improvement of prognosis to evaluate the development degree of the right ventricle comprehensively and accurately.At present,it is generally believed that the most effective treatment strategy can be obtained by classifying the development degree of the right ventricle in morphology.The surgical treatment has developed from early surgical pulmonary bypass to the interventional and hybrid surgery,which greatly improves prognosis and reduces surgical trauma.Among them,the pereutaneous pulmonary valve radiofrequency perforation plus balloon dilation and PDA stent implantation can be used as the preferred treatment for PA/IVS with dysplasia of the right ventricle.Particularly,PA/IVS can be cured with the interventional surgery alone for children with mild or even moderate dysplasia of the right ventricle.Hybrid surgery that significantly reduces trauma compared with traditional surgery is also an important choice for the areas where interventional surgery is relatively outdated.This article reviews and summarizes the progress of recognition and surgical treatment of PA/IVS,in order to provide reference for the clinical diagnosis and treatment.

Expression and effects of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 1 and 2 in the denervated skeletal muscle of rats / 中国组织工程研究

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) are involved in the remodeling of extracellular matrix under normal or pathological conditions, and the positive expression of MMP-2 and MMP-9 has been shown to play important physiological and pathological roles in the denervated skeletal muscle. OBJECTIVE: To investigate the expression and effect of MMP-2 and MMP-9 and their tissue inhibitors (TIMP-1 and TIMP-2) in the denervated skeletal muscle. METHODS: The right sciatic nerve of rats was cut off to establish the model of denervated skeletal muscle, and the right skeletal muscle of rats was harvested after different intervals. The morphologic changes of the denervated skeletal muscle were detected through hematoxylin-eosin staining, immunohistochemical staining, and RT-PCR. The expression and change of MMP-2 and MMP-9 and TIMP-1 and TIMP-2 were compared with the sham operation group. RESULTS AND CONCLUSION: Atrophy and fibrosis were observed in the denervated skeletal muscle. There was a rapid increase of MMP-2 and TIMP-2 with double peaks at the 3rdand 56thdays after modeling; at the 3rdand 70thdays, the expression of MMP-9 increased significantly and reached the peak respectively; mRNA level of TIMP-1 only increased in the early stage, reached the peak at the 3rdday and gradual declined to normal level, without the second peak. To conclude, MMPs and TIMPs are involved in the tissue changes following denervation. TIMP-1 and TIMP-2 have a protective role in the remodeling progression. The altered balance between MMPs and TIMPs in the late stage of denervation may be responsible for extracellular matrix degradation leading to the atrophy and fibrosis progression.

Transposition of Branches of Radial Nerve Innervating Supinator to Posterior Interosseous Nerve for Functional Reconstruction of Finger and Thumb Extension in 4 Patients with Middle and Lower Trunk Root Avulsion Injuries of Brachial Plexus / 华中科技大学学报（医学）（英德文版）

This study aimed to investigate the reconstruction of the thumb and finger extension function in patients with middle and lower trunk root avulsion injuries of the brachial plexus.From April 2010 to January 2015,we enrolled in this study 4 patients diagnosed with middle and lower trunk root avulsion injuries of the brachial plexus via imaging tests,electrophysiological examinations,and clinical confirmation.Muscular branches of the radial nerve,which innervate the supinator in the forearm,were transposed to the posterior interosseous nerve to reconstruct the thumb and finger extension function.Electrophysiological findings and muscle strength of the extensor pollicis longus and extensor digitorum communis,as well as the distance between the thumb tip and index finger tip,were monitored.All patients were followed up for 24 to 30 months,with an average of 27.5 months.Motor unit potentials (MUP) of the extensor digitorum communis appeared at an average of 3.8 months,while MUP of the extensor pollicis longus appeared at an average of 7 months.Compound muscle action potential (CMAP) appeared at an average of 9 months in the extensor digitorum communis,and 12 months in the extensor pollicis longus.Furthermore,the muscle strength of the extensor pollicis longus and extensor digitorum communis both reached grade Ⅲ at 21 months.Lastly,the average distance between the thumb tip and index finger tip was 8.8 cm at 21 months.In conclusion,for patients with middle and lower trunk injuries of the brachial plexus,transposition of the muscular branches of the radial nerve innervating the supinator to the posterior interosseous nerve for the reconstruction of thumb and finger extension function is practicable and feasible.

TGF-β1-induced synthesis of collagen fibers in skeletal muscle-derived stem cells / 华中科技大学学报（医学）（英德文版）

The aim of this study was to investigate the mechanism of deposition of extracellular matrix induced by TGF-β1 in skeletal muscle-derived stem cells (MDSCs). Rat skeletal MDSCs were obtained by using preplate technique, and divided into four groups: group A (control group), group B (treated with TGF-β1, 10 ng/mL), group C (treated with TGF-β1 and anti-connective tissue growth factor (CTGF), both in 10 ng/mL), and group D (treated with anti-CTGF, 10 ng/mL). The expression of CTGF, collagen type-I (COL-I) and collagen type-III (COL-III) in MDSCs was examined by using RT-PCR, Western blot and immunofluorescent stain. It was found that one day after TGF-β1 treatment, the expression of CTGF, COL-I and COL-III was increased dramatically. CTGF expression reached the peak on the day 2, and then decreased rapidly to a level of control group on the day 5. COL-I and COL-III mRNA levels were overexpresed on the day 2 and 3 respectively, while their protein expression levels were up-regulated on the day 2 and reached the peak on the day 7. In group C, anti-CTGF could partly suppress the overexpression of COL-I and COL-II induced by TGF-β1 one day after adding CTGF antibody. It was concluded that TGF-β1 could induce MDSCs to express CTGF, and promote the production of COL-I and COL-III. In contrast, CTGF antibody could partially inhibit the effect of TGF-β1 on the MDSCs by reducing the expression of COL-I and COL-III. Taken together, we demonstrated that TGF-β1-CTGF signaling played a crucial role in MDSCs synthesizing collagen proteins in vitro, which provided theoretical basis for exploring the methods postponing skeletal muscle fibrosis after nerve injury.

TGF-β1-induced synthesis of collagen fibers in skeletal muscle-derived stem cells / 华中科技大学学报（医学）（英德文版）

The aim of this study was to investigate the mechanism of deposition of extracellular matrix induced by TGF-β1 in skeletal muscle-derived stem cells (MDSCs). Rat skeletal MDSCs were obtained by using preplate technique, and divided into four groups: group A (control group), group B (treated with TGF-β1, 10 ng/mL), group C (treated with TGF-β1 and anti-connective tissue growth factor (CTGF), both in 10 ng/mL), and group D (treated with anti-CTGF, 10 ng/mL). The expression of CTGF, collagen type-I (COL-I) and collagen type-III (COL-III) in MDSCs was examined by using RT-PCR, Western blot and immunofluorescent stain. It was found that one day after TGF-β1 treatment, the expression of CTGF, COL-I and COL-III was increased dramatically. CTGF expression reached the peak on the day 2, and then decreased rapidly to a level of control group on the day 5. COL-I and COL-III mRNA levels were overexpresed on the day 2 and 3 respectively, while their protein expression levels were up-regulated on the day 2 and reached the peak on the day 7. In group C, anti-CTGF could partly suppress the overexpression of COL-I and COL-II induced by TGF-β1 one day after adding CTGF antibody. It was concluded that TGF-β1 could induce MDSCs to express CTGF, and promote the production of COL-I and COL-III. In contrast, CTGF antibody could partially inhibit the effect of TGF-β1 on the MDSCs by reducing the expression of COL-I and COL-III. Taken together, we demonstrated that TGF-β1-CTGF signaling played a crucial role in MDSCs synthesizing collagen proteins in vitro, which provided theoretical basis for exploring the methods postponing skeletal muscle fibrosis after nerve injury.

Application of fast-track surgery in the management of patients with esophageal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the influence of fast-track surgery in perioperative period on the clinical outcomes of patients with esophageal cancer.</p><p><b>METHODS</b>Clinical data of 117 patients with esophageal cancer between January 2011 and June 2011 were retrospectively analyzed. Sixty-three cases (study group) were treated with fast-track surgery and 54 cases(control group) were treated according to routine protocol in the perioperative period.</p><p><b>RESULTS</b>The operative time, time to drainage tube removal, and length of hospital stay were significantly shorter in the study group than those in the control group(all P<0.05). Compared with the control group, the medical cost was lower(P<0.05). The overall postoperative complication rate was 7.9% in the study group and 24.1% in the control group(P<0.05).</p><p><b>CONCLUSION</b>Fast-track surgery in the perioperative period for patients with esophageal cancer can promote bowel function recovery and decrease morbidity.</p>